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Coming dissertations at MedFak

  • Overcontrol in anorexia nervosa : assessment, occurrence, and treatment Author: Martina Isaksson Link: Publication date: 2021-03-26 12:59

    Excessive overcontrol – characterized by high risk aversion, compulsiveness, emotion inhibition, and social deficits – has been suggested to be a core mechanism for developing and maintaining anorexia nervosa. However, such factors are rarely targeted as key elements in treatment of the disorder. The overall aim of this thesis was to evaluate the occurrence of over- and undercontrolled personality styles in patients with eating disorders, and to evaluate the treatment effects and patient experiences of Radically open dialectical behavior therapy (RO DBT) for outpatients with anorexia. In a cross-sectional study (Study I) with two non-clinical samples (n = 483 and n = 197), psychometric evaluations showed that a new shortened version of the Ego Undercontrol Scale (EUC-13), measuring over- and undercontrol, and the Ego Resilience Scale (ER) measuring adaptive control, seemed promising for assessing the constructs. In a cross-sectional study (Study II) assessing the occurrence of overcontrol in a clinical and non-clinical population, findings showed that overcontrol was more common in restricting anorexia (n = 34) and atypical anorexia (n = 29), than in bulimia (n = 76), borderline personality disorder (n = 108), and a non-clinical sample (n = 444). Anorexia with binge eating and purging (n = 31) showed similar, but somewhat lower, levels of overcontrol compared with atypical and restricting anorexia. However, differences from the other eating disorder groups were not significant. In a single-case experimental design study with 13 patients (Study III), the effect of RO DBT – a treatment developed for disorders related to excessive overcontrol – was evaluated for outpatients with mild to moderate anorexia. Findings were that all completers (62%) were in remission after treatment, and that the treatment clinically and reliably reduced eating disorder psychopathology and clinical impairment, and increased quality of life. In a qualitative interview study (Study IV), 11 participants from Study III reported that they appreciated the comprehensive approach, where both the eating disorder and the overcontrol were addressed, and that sharing with others was important. Findings indicated that the EUC-13 and the ER seemed promising for assessing overcontrol, undercontrol, and resilience. The occurence of overcontrol in different types of AN raised questions regarding if treatment of AN would be more effective if these difficulties were addressed. Lastly, preliminary evidence showed that outpatient RO DBT could be effective for patients with mild to moderate AN and overcontrol, and that the treatment was well received by the patients. 

  • Nitric oxide within the concept of united airway disease : Exhaled and nasal nitric oxide in cystic fibrosis, asthma and upper airway inflammatory diseases Author: Christina Krantz Link: Publication date: 2021-03-19 08:30

    Background: Within the concept of united airway disease, it is postulated that inflammatory disorders in the upper and lower airways are interrelated and influence each other. Fractional exhaled nitric oxide (FeNO) is an established biomarker of type-2 inflammation in the lower airways and is elevated in patients with asthma. However, the relation between nasal nitric oxide (nNO) and upper airway inflammation is less clear. Although cystic fibrosis (CF) is associated with increased airway inflammation, nitric oxide is not elevated in patients with CF.

    Aims: To study nNO and FeNO as biomarkers of type-2 inflammation in the upper and lower airways, respectively, in relation to symptoms, disease control and treatment of both upper and lower airway diseases, and in relation to systemic inflammation.

    Methods: This thesis is based on the MIDAS cohort of children and young adults with asthma (n=411) with a follow-up after 2-5 years (n=258), as well as one cohort of children and adults with CF (n=38) and one multicentre population-based cohort of middle-aged adults (n=5,824). Cross-sectional (Paper I-IV) and longitudinal (Paper III) analyses were performed. The main outcomes were nNO (Paper I-III) and FeNO (Paper II and IV) and their relations to IgE sensitisation, upper and lower airway symptoms and treatment, and systemic inflammation.

    Results: In subjects with asthma, nNO was associated with FeNO and increased bronchial responsiveness and nNO was higher in subjects with perennial sensitisation. In non-asthmatic middle-aged subjects with perennial sensitisation, rhinitis and rhinoconjunctivitis were associated with higher FeNO. There was also a positive interaction with perennial sensitisation for the relation between upper airway inflammatory disorders and FeNO. Treatment with nasal or inhaled corticosteroids was associated with lower nNO levels in subjects with asthma. In middle-aged subjects with asthma and perennial sensitisation, use of nasal corticosteroids related to lower FeNO, whereas use of inhaled corticosteroids related to higher FeNO levels. Patients with CF had lower levels of nNO and FeNO than controls. Moreover, lower FeNO levels were associated with lower lung function and higher blood neutrophil counts in CF.

    Conclusion: Within the concept of united airway disease, nNO is related to lower airway inflammation, responsiveness and treatment, and FeNO is related to upper airway inflammatory disorders, with a significant interaction with perennial sensitisation. In CF, lower FeNO is related to more severe disease with lower lung function and more systemic inflammation.

  • Alzheimer's Disease Neuropathological Change and neuronal and glial alterations in patients with idiopathic Normal Pressure Hydrocephalus Author: Sylwia Libard Link: Publication date: 2021-03-05 09:38

    Alzheimer’s disease Neuropathological Change (ADNC), i.e. amyloid β (Aβ) and hyperphosphorylated τ (HPτ), is seen in excess in the brains of subjects with AD. Idiopathic Normal Pressure Hydrocephalus (iNPH) lacks defined hallmark lesions, affects the elderly and leads to cognitive impairment, gait disturbance and urinary incontinence that can be treated with a ventriculoperitoneal shunt (VPS). A few centres around the world have obtained a brain biopsy from the area of VPS. It has been reported that the presence of ADNC in the biopsy is associated with progression to AD.

    We confirm that majority of iNPH subjects display ADNC, and the ADNC increases in extent with age, in line with AD. The HPτ pathology is sparse in majority of cases. We observed remarkable neuronal survival and loss of matrix/synapses in subjects with iNPH (paper III).

    When studying subjects with notable Aβ pathology (paper IV), we observed a stepwise increase of pyroglutamylated Aβ (pyAβ) and phosphorylated Aβ variants in iNPH. These two Aβ variants are associated with symptomatic AD and correlate with HPτ pathology. The pyAβ in the frontal cortex is a predictive marker for AD. Thus, notable Aβ pathology in presence of HPτ in iNPH is suggestive of a moderate level of ADNC.  

    When assessing changes in the extent of pathology occurring during 21 months in a frontal cortex of a subject with iNPH and AD (paper II), HPτ pathology increased in parallel with neuronal and synaptic loss, whereas Aβ pathology and astroglial activity were stable over time. In contrast, we observed reduction of microglial markers, which might explain why anti-inflammatory treatment is effective only at an early stage of AD.

    When assessing brain tissue, the section thickness must be standardised, as it affects the staining outcome and diagnosis (paper I).

    In conclusion, we have demonstrated a progressive neurodegeneration of ADNC type in a population of iNPH subjects, mimicking what is seen in subjects with AD. A brain biopsy obtained from subjects with iNPH should be obligatory. This is because when ADNC is present in the biopsy, representing prodromal AD, contact with memory clinic should be initiated.